Expression Of Rage In Diabetic Rat Kidney Tissue: Relation Between Rage And Podocyte Injury

Objective: To evaluate the changes of RAGE(receptor for advanced glycation endproducts) expression in renal tissue of diabetic rats and control rats, and explore the clinical significance of the different expression of RAGE.Methods: Adult (aged 8 weeks) male Wistar rats were injected intravenously with streptozotocin (STZ) at a dose of 55mg/kg body wt in citrate buffer to induce diabetes(n=18). Control rats received an intravenous injection of citrate buffer alone (n=8). The rats were sacrificed eight weeks after the induction of diabetes. The renal RAGE and desmin expressions were accessed by semi-quantitative immunohistochemistry. The quantitative analysis of staining intensity was carried out by MCID Analysis Evaluation 7.0 image analysis process. Light microscopic views (PAS × 400) were scanned into a computer .The quantification of areas of 10 glomeruli from each animal selected at random were also performed using MCID Analysis Evaluation 7.0 image analysis process. Meanwhile the podocyte numbers of the 10 glomeruli were calculated. Podocyte number of each glumerulus was accessed by the average value of podocyte number per 1000μm~2 aera of glomeruli.Values are expressed as mean±SD. Statistical significance was evaluated by Independent -Samples T test for comparison. All statistical testswere performed on raw data by SPSS 10.0 process. Rigit analysis was used to evaluate the grade datas. And correlation analysis was used to evaluate the relationship between RAGE-positive cell infiltration and desmin damage score, GHb, fluorescene intensivity of AGEs, 24hUP, podocyte number of each glomerulus and Ccr. P<0.05 was considered significant.Results:1 .RAGE and desmin were detected in renal tissues from both diabetic and nondiabetic rats.2. The expressions of RAGE and desmin are definitely higher in diabetic rats than in control rats.3. Compare with control rats, the podocyte number of each glomerulus was decreased significantly (PO.01), and the expression of RAGE and desmin were increased remarkably in diabetic rats (PO.01) .There was a relationship between immunostaining for RAGE and the podocyte number of each glomerulus in diabetic rats (P<0.01) .Conclusion:The expression of RAGE is observed in physical condition. The diabetic milieu induces or upregulates RAGE expression in glomeruli. Furthermore, the extent of RAGE expression in glomeruli closely correlated with GHb(r=0.838, P<0.01), the fluorescene intensivity of AGEs(r=-0.746, P<0.Ql), podocyte number of each glumerulus (r=-0.736vP<0.01). These findings suggest that RAGE may play an important role in the progression of diabetic nephropathy (DN) , and in control of high blood glucose may decrease the incidence of DN.